The goals of Core D (Neuropathology) are to perform postmortem neuropathologic evaluations of participants in the Udall Center. In addition, Core D will provide neuropathologic support to research projects, in particular tau biochemical support and immunohistochemistry for Project 2 , as well as tissue processing and histology for Project 3. Core D will also assist Project 3 with electron microscopic studies. To accomplish these objectives, the specific aims of Core D will: Specific Aim 1. Perform standardized diagnostic neuropathologic evaluations and data collection on all brains harvested locally or sent to the Udall Center by referring physicians, with particular focus on cases followed by Core B. This will include a) immunostaining of cortical, hippocampal and basal forebrain sections for a-synuclein to record density of Lewy bodies in multiple cortical regions; b) characterizing non-Lewy body Parkinsonian degenerative disorders with immunocytochemistry, including antibodies to tau, TDP-43, ubiquitin, FUS, a-internexin and aB-crystallin, recording estimates of neuronal and glial lesions in neocortex, hippocampus, basal ganglia, thalamus, subthalamic nucleus, midbrain, pons, medulla and cerebellar dentate nucleus for cases with tauopathy; c) assessing Alzheimer type pathology with counts of senile plaques and neurofibrillary tangles in multiple cortical and subcortical areas with thioflavin-S fluorescent microscopy, and assign a Braak neurofibrillary tangle stage on all cases; and d) using validated neuropathologic research criteria for those disorders for which such criteria have been established and best clinical practice for uncommon disorders for which research criteria do not yet exist. Specific Aim 2. Provide frozen human brain samples or DNA to investigators in the Udall Center, particulady Projects 1 and 2, as well as to qualified investigators at other research institutions. Specific Aim 3. Assist Projects 2 with biochemical studies of tau protein in human brain samples. Specific Aim 4. Assist Project 3 with neuropathologic characterization of mouse models subjected to drug treatments and with electron microscopic support to evaluate effects of drugs on tau and a-synuclein fibrillization. RELEVANCE (See instructions): The gold standard for diagnosis of neurodegenerative disorders, such as Parkinson disease (PD), is neuropathology, which is the medical specialty that uses microscopic evaluation of tissue changes to arrive at a diagnosis. Accurate diagnosis is critical to finding genes and other factors that cause PD, which are the first steps in the process of finding a cure for PD and related disorders.